LAUSR

IntroductionUp to 30% of all human cancers are driven by the overactivation of RAS signaling. Son of Sevenless 1 (SOS1) is a central node in RAS signaling pathways and modulation of SOS1-mediated RAS activation represents a unique opportunity for treating RAS-addicted cancers. Several recent publications and patent applications have demonstrated the ability of small molecules to affect the activation of RAS by SOS1 and have shown their potential for the treatment of cancers driven by RAS mutants.Areas coveredPatent documents focusing on both small molecule inhibitors and activators of the SOS1:RAS interaction and their potential use as cancer therapeutics are covered. A total of 10 documents from 4 applicants are evaluated with discussion focusing on structural modifications of these small molecule inhibitors as well as relevant preclinical data.Expert opinionThe last decade has seen a significant increase in research and disclosures in the development of small molecule SOS1 inhibitors. Considering the promising in vitro and in vivo data that have been disclosed, interest in this area of research will likely remain strong for the foreseeable future. With the first SOS1 inhibitor currently in phase I clinical trials, the outcome of these trials will likely influence future drug development of SOS1 inhibitors for treatment of RAS-driven cancers.